For viruses such as the herpes viruses, which contain a cell-derived lipid envelope, the virally-encoded envelope proteins are the primary determinants of tissue tropism and the mediators of virus entry, cell to cell spread and maturation of virus particles. Human cytomegalovirus (CMV), a member of the Herpesviridae family, is a significant opportunistic pathogen responsible for serious clinical consequences in a variety of immunosuppressed patient groups such as neonate and infants, persons with AIDS and individuals undergoing immunosuppressive regimes for the purpose of organ or bone marrow transplantation. As is true for other human herpes viruses, CMV establishes a life-long latent infection with its human host and is ubiquitous in the population with upwards of 75% infectivity rate found in the United States. At present there is no protective vaccine. Currently available antiviral drugs which target viral DNA replication are efficacious but exhibit significant host toxicity and a high spontaneous resistance rate. Thus, there is a tremendous need to identify alternative drug targets and immunogens that elicit protective immunity.